tbuckley/cabot-search huggingface dataset:
Evaluation of the prevalence of HPV from environmentally unfavorable districts of the Republic of Karakalpakistan.
Authors: Nargiza Nematovna Zakhirova, Mirzagaleb Tillyashaykhov, Daniyar Nishanov, Viloyat Saydakhmedova, Elnara Osmanova, Khurshid Islamov
Journal: Journal of Clinical Oncology (2023)

e17526 Background: Identification of HPV-positive women in the Aral regions of the Republic of Karakalpakstan and the city of Chirchik, Tashkent region. Methods: The study included 48,788 women aged 30-55 years.The project was approved by the Ministry of Health of the Republic, covering 10 districts, mainly near the Aral Sea: Khojeyli, Kanlykul, Shumanay, Chimbay, Karauzyak, Kungrad, Kegeili, Muynak, Buzatau, Nukus district. The Xpert HPV Assay is a qualitative in vitro diagnostic test for the detection of the E6/E7 region of high oncogenic risk human papillomavirus (HPV) genomic DNA in patient specimens. The analysis was performed on a Cepheid Gene Xpert system. The Xpert HPV test specifically identified HPV 16 and HPV 18/45 types in two separate detection channels and reported the presence of 11 other high risk virus types (31, 33, 35, 39, 51, 52, 56, 58, 59, 66 and 68) as a combined result. Results: Of these, HPV was detected in 3304 (6.8%) women, HPV-negative women were 45.484 (93.2%). Distribution by HPV types: among HPV-positive women HPV 16 - 28%; HPV 18.45-7.6%; HPV 31.33.35.52-23.9%; HPV 51-11.6%; HPV 39.56.66-18.4%; mixed forms - 10.2%. Erroneous tests were 2.9%. The age of HPV positive women was 35-45 years. Conclusions: In the studied regions, HPV types 16,31,33,35,52 were most often detected, which should be taken into account when developing the country's national screening program. Also, given the age-specific prevalence of HPV, may be considered for the target group of cervical cancer screening of women aged 35 and 45 years, which is more acceptable for a developing country.
Patterns of recurrence post prostatectomy in the PSMA era: What lessons can we take to daily practice from a high-volume nuclear medicine center?
Authors: Dr. Paulo Sergio Lages, Luciano Monteiro do Prado Junior, Leonardo Fonseca Monteiro do Prado, Michelle Barbosa, Paulo Gustavo Bergerot, Pamela Carvalho Muniz, Luciana Lages, Diogo Augusto Rodrigues Rosa, Mariane Fontes Dias, Cristiano Augusto Andrade de Resende, Maria Fernanda Inocente Messias Pinheiro, Daniel Vargas Pivato de Almeida
Journal: Journal of Clinical Oncology (2023)

e17013 Background: PSMA has deeply modified the treatment of prostate cancer, mainly in the biochemical recurrence setting, where the therapeutic plan may be changed in up to two thirds of cases. Unfortunately, this diagnostic tool is still not fully available in many places over the world. Growing evidence from high-volume nuclear medicine centers may guide the development of adapted treatment plans based on sites of relapse according to wide available clinical information. Methods: We retrospectively reviewed 648 Ga68-PSMA-PET-CT scans in the biochemical relapse setting in patients initially treated with prostatectomy. Results were classified either as negative or positive if abnormal SUV uptake was detected in the prostate bed, pelvis, or distant organs. We then classified the patients with positive tests based on sites of relapse according to serum PSA level. Results: Among the 648 analyzed patients, there were 60, 63, and 61 recurrences in prostate bed, pelvis, or distant organs, respectively. For those with serum PSA ≤ 1.0 ng/mL, there was a higher chance of locoregional failure (prostate bed or pelvis), with less than 20% presenting distant metastasis. When assessing patients with serum PSA 1.1-2.0 ng/mL, the rate of distant metastasis increased to 22.7%, while it was found in 40.7% of patients with serum PSA between 2 and 5 ng/mL. Conclusions: PSMA-PET-CT scan is clearly modifying the therapeutic landscape of prostate cancer in different scenarios. Although it is not available in many regions due to high financial costs and logistic barriers, the emerging evidence arising from specialized cancer centers matching the clinical information with tests results may help doctors to make better treatment decisions even without PSMA-PET-CT scans. [Table: see text]
Early onset gastric cancer: An analysis of epidemiological and environmental risk factors.
Authors: Erfan Zarrinkhoo, Shreya Condamoor, Kyle D. Klingbeil, Joon Park, Nicholas Jackson, Victor Yundeh Chiu, Brian E. Kadera
Journal: Journal of Clinical Oncology (2023)

e16103 Background: Gastric cancer is the fourth most common malignancy in the world and the second leading cause of cancer related deaths. Its overall incidence has decreased in recent years, but recent data suggests that its rate has actually been increasing specifically amongst younger adults. Emerging data suggests that it is the combination of biological risk factors and environmental triggers that are the cause for this increasing rate. There has been increased interest in studying early onset gastric cancer (EOGC) as a proxy for understanding the genetic alterations that lead to gastric cancer at any age. However, understanding the environmental factors that lead to the development of cancer at a younger age is an area of study that requires more exploration. In this study, we investigate the epidemiology, environmental risk factors and common presenting symptoms associated with early onset gastric cancer patients. Methods: This is a retrospective cohort study of 174 patients with newly diagnosed gastric adenocarcinoma at three safety net hospitals in Los Angeles between 2010 and 2022. The patients were divided into two groups, with an age cutoff of 45 years old for early onset gastric cancer. We compared the rates of smoking, alcohol use, infection with H pylori and gender between the two groups. The stage at time of presentation, rates of misdiagnosis, presenting symptoms, and mortality rates were also compared. Results: There was no statistically significant difference (p &lt; 0.05) in rates of smoking, alcohol use, and H. pylori infection between the groups. However, patients with early onset gastric cancer were 10% more likely to be misdiagnosed, and 6% more likely to present with metastatic disease. They were also 16% more likely to be female, 17% more likely to be Hispanic, and 22% more likely to expire compared to patients older than 45. An analysis conducted on patients’ presenting symptoms indicated that hematemesis was much more likely to be associated with patients less than 45 to a statistically significant level (p = 0.035). Conclusions: Based on our findings, EOGC was more likely to be seen in females and Hispanic populations. Additionally, no risk factors were identified to be more closely associated with either cohort. EOGC patients were more likely to be misdiagnosed and therefore present with advanced disease, leading to higher rates of mortality. Further investigation into both genetic alterations and environmental factors associated with early onset gastric cancer is warranted, as this holds important implications for patients regarding diagnosis, treatment, and overall outcomes.
Proteomic profiling of FOLFOX-resistant colorectal cancer cells.
Authors: Shing Yau Tam, Md Zahirul Islam Khan, Jerica Hiu Yui Yip, Hong Yiu Yan, Tsz Yan Tam, Helen Ka Wai Law
Journal: Journal of Clinical Oncology (2023)

e15588 Background: Chemoresistance is a major cause of colorectal cancer (CRC) mortality. Although multidrug regimen has been established as the backbone of CRC chemotherapy for better treatment efficacy, chemoresistance is common among late-stage CRC. Proteomic profiling of both the chemoresistant and wild-type CRC cells may provide hints for the mechanisms of chemoresistance and suggest targets for improving chemotherapy efficacy. Methods: Human CRC cell lines (DLD-1 and HCT-116) were treated with progressively increased dosage of FOLFOX (5-flurouracil (5-FU), folinic acid (LEU) and oxaliplatin (OXA)) to develop chemoresistance as DLD-1-R and HCT-116-R respectively. After confirmation of the successful development of chemoresistance by Cell Counting Kit-8 test (CCK-8), the comparison of cell samples between chemoresistant and wild-type cell lines were conducted by proteomic profiling using quantitative mass spectrometry (MS)-based techniques. MS and MS/ MS peptides spectra were analysed by Progenesis QI for proteomics software compared with Swiss-Prot dataset. Differentially expressed proteins (DEP) are defined as -1 &gt; log2FC &gt; 1, p &lt; 0.05. Gene-list enrichment by Enrichr (https://maayanlab.cloud/Enrichr/) was employed for identifying the hallmark gene sets of the significantly enriched molecular processes and pathways of each group. All experiments were performed with at least 3 replications. Results: The development of FOLFOX-resistance took one year. The highest drug concentrations achieved were 0.5mM 5-FU, 50µM LEU, and 50µM OXA for DLD-1-R, and 5µM 5-FU, 0.5µM LEU, and 0.5µM OXA for HCT-116-R. The chemoresistance was found to be 14.73 (DLD-1-R) and 1.61 (HCT-116-R) times of the wild-type DLD-1 and HCT-116 respectively from CCK-8 tests. A total of 345 DEP with 154 up-regulated and 191 down-regulated proteins were found in DLD-1-R. While a total of 95 DEP with 66 up-regulated and 29 down-regulated proteins were found in HCT-116-R. Gene ontology molecular process (2021) analyses found that cadherin binding were significantly enriched in both DLD-1-R and HCT-116-R (Adjusted p-value &lt; 0.05). KEGG pathway (2021) analysis found that oxidative phosphorylation, regulation of actin cytoskeleton and HIF-1 signalling pathway are among the significantly enriched pathways in DLD-1-R (Adjusted p value &lt; 0.05). There was no significantly enriched pathway found in HCT-116-R in the same analysis. Conclusions: Our study has successfully established CRC cells with chemoresistance to the FOLFOX regimen. Proteomic profiling has found the cadherin binding as the significantly altered molecular process along with several important signalling pathways in chemoresistant CRC cells. These findings could suggest new directions in the development of anti-chemoresistance strategies of CRC.
Transcatheter-directed Y-90 radioembolization compared with chemoembolization for the treatment of hepatic metastases from colon cancer.
Authors: Peter Young, Brittany Miles, Brittany Dang, James David Mackey
Journal: Journal of Clinical Oncology (2023)

e15620 Background: Arterially directed embolic therapy has been a mainstay in the management of hepatic malignancy of both primary and metastatic origin. The benefits of transcatheter-directed Yttrium-90 radioembolization (TARE) and chemoembolization (TACE) in conjunction with systemic therapy are well documented, though only TARE is currently recommended for the management of hepatic metastases from colon cancer. We evaluated patients who underwent TARE or TACE to assess survival rates at 2 years post-procedure. Methods: The TriNetX Diamond network was used for this study. TriNetX provides access to anonymized medical record information on more than 213 million patients in 92 large healthcare organizations. Two cohorts of patients were created utilizing International Classification of Disease-10 (ICD-10) codes. All patients were required to have colon cancer (C18), liver metastases (C78.7), and liver-directed treatment (CPT code 37243). One cohort received chemoembolization (CPT 96420) while the other received Yttrium-90 microspheres (CPT 79445). The cohorts were balanced for age, race, gender, and ethnicity, resulting in 336 patients in each arm. They were then evaluated for risk of death at two years. Results: Patients who received Y-90 had a risk ratio for death of 1.23 compared to patients treated with chemoembolization. Figure 1. Conclusions: Patients who underwent TARE were at a significantly higher risk of mortality at 2 years post-procedure compared to those who underwent TACE. As only Y-90 radioembolization is currently recommended under NCCN guidelines for the treatment of hepatic metastatic lesions from colon cancer, we hope to further discussion among specialists to determine whether TACE may provide an alternative treatment option. [Table: see text]
Demographic factors affecting patients with AML with myelodysplasia-related changes.
Authors: Laura Stewart, Darby Keirns, Xinxin Wu, Peter T. Silberstein, Beau Hsia
Journal: Journal of Clinical Oncology (2023)

e19027 Background: Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a rare and aggressive form of acute myeloid leukemia (AML) that makes up about 25-34% of its annual cases. The subtype includes a varied group of tumors with clinical, genetic, and morphological characteristics that confer poor outcomes. AML-MRC is commonly treated with intensive chemotherapy, but the median survival is only 9-12 months. Given the poor outcomes, gaining a better understanding of epidemiologic factors could reveal opportunities for earlier diagnosis and improved treatment planning. Demographic characteristics of AML-MRC patients were identified and examined using the National Cancer Database (NCDB). Methods: Individuals with a confirmed diagnosis of AML-MRC (N = 14,536) were identified using the NCDB for a retrospective analysis from 2004 to 2020. Patient sex, age at diagnosis, race, household income, insurance status, urban/rural residence, and Charlson-Deyo score were examined by descriptive statistics, and diagnostic trends by year were identified and calculated with regression analysis. Results: A total of 14,536 patients diagnosed with AML-MRC between 2004 – 2020 were identified in the NCDB. Within this timeframe, there was an increasing incidence of diagnosis per year (R2 = 0.9). AML-MRC was more common in males (61.1%) than females (38.9%), and the average age at diagnosis was 68.9 years (SD = 13.0, range = 0 – 90 years). The majority of patients (87.3%) were White. Patients were most likely to be a part of the highest median household income quartile (33.6%) and least likely to be a part of the bottom quartile (13.2%). A higher percentage of patients were insured by Medicare (63.0%) compared to private insurance (25.3%). Most patients lived in counties in metro areas of 1 million population or more (51.4%). Most individuals had Charlson-Deyo comorbidity scores of zero (68.1%). The most common type of treatment facility was academic/research programs (55.1%) followed by comprehensive community cancer programs (23.3%). Conclusions: AML-MRC is a common subtype of AML with a poor prognosis. Previous studies have found that most individuals with AML-MRC are older-aged, White males. Our study corroborated this finding and examined additional demographic factors. We found that these patients were more likely to hold insurance through Medicare, likely reflecting the older average age at diagnosis. Additionally, patients were most commonly in the highest household income quartile and living in a metropolitan area with the highest population density. This could suggest that better access to healthcare improves rates of diagnosis of AML-MRC. Especially given that more people are being diagnosed each year, further research should work to understand the effects of these, and other, socioeconomic factors on the diagnosis, treatment, and prognosis of patients with AML-MRC.
Real-world genetic testing patterns in metastatic prostate cancer in Latin American (LATAM) population.
Authors: Martin Angel, Berenice Freile, Andres Rodriguez, Federico Cayol, Ray Manneh Kopp, Patricia Rioja, Federico Losco, Laura Bernal Vaca, Jose Mauricio Penaloza, Maycos Leandro Zapata Muñoz, Silvia P. Neciosup, Juan Pablo Sade
Journal: Journal of Clinical Oncology (2023)

e17055 Background: Prostate cancer (PC) clinical course is variable. It was thought that BRCA1 and BRCA2 mutations were associated with only a small proportion of PC cases. However, recent genomic analysis has revealed that germline or somatic inactivating mutations in genes involved in the homologous recombination (HR) pathway of DNA repair collectively occur in as much as 20%-25% of advanced PC. Referring to the metastatic castration resistant PC (mCRPC) the somatic mutations were recently reported to be up to 12,7% for BRCA2 and 2% for BRCA1. PC is the most frequent tumor among LATAM men. The incidence of de novo metastatic PC is higher in LATAM than other parts of the world, and demographic changes in the region have increased disease burden. However, region-specific information about genomic profiling of this tumor is scant. This study aims to describe the genomic profile patterns of PC, either presenting as metastatic hormone treatment–naive prostate cancers, or locoregional tumors that later evolve to metastatic disease in LATAM pts. Methods: A retrospective observational cohort design was used. The study sample included patients with a confirmed PC diagnosis with adenocarcinoma histology, from 8 academic centers in 3 countries between 1 st January 2020 and 30 th November 2022 whom had been molecularly tested. Results: Of 185 pts tested, 183 had metastatic PC. Somatic evaluation was done in 49.5% of the pts, while 66.48% have germline test, 13% pts were tested by both methods. Forty-two (22.7%) pts were tested in the metastatic sensitive castration scenario, instead 141 (76.2%) were mCRPC. Actionable mutations were detected in 21 pts (11.35%), being the most frequents PTEN and BRCA2. The median tumor mutational burden was 5 (IQR 0-2.52). No mutation in the following clinically relevant genes were found in our pts: BRCA1, RAD51C, RAD51D, RAD54, PALB2 and BRIP1 (Table1). Between pts with actionable mutations, 27.3% had high volume disease, with a median Gleason score of 9 (IQR 8-9) and de novo metastatic setting in 40.9%. Despite that 25.9% of our pts have a VUS (Variant of unknown significance), only 7 pts (3.8%) access to oncology genomic counseling. Conclusions: In our region, the percentage of actionable mutations found in this population appears to be lower than that reported in studies from other regions of the world, but remarkably the mutations detected are different. This data shows the importance to have mutational data of the population of each region what is heterogeneous among themselves and with respect to other regions of the world. [Table: see text]
Phase 1, randomized, open-label, single-dose, crossover study to evaluate the bioequivalence of four formulations of oral rivoceranib tablets in healthy subjects.
Authors: Janelle Weyer, Xianzhang Meng, Lynda Finis, Bill Strickland, CheolHee Park, Seong Jang
Journal: Journal of Clinical Oncology (2023)

e15122 Background: Rivoceranib is a novel oral tyrosine kinase inhibitor that potently and selectively inhibits VEGFR2. Rivoceranib is being investigated for indications targeted towards solid malignancies as either monotherapy or in combination with other anticancer therapies. Herein, we assessed the bioequivalence of a single dose of rivoceranib administered as 4 different formulations in healthy subjects. Methods: This single-center, open-label, randomized, single-dose, 4-way crossover study evaluated the bioequivalence of 4 different formulations of rivoceranib oral tablets in healthy adults. Each subject participated in 4 treatment periods, where they were randomized to 1 of 4 sequences: ABCD, BDAC, CADB, and DBAC (Formulation A = rivoceranib 250 mg tablet/clinical formulation used in the pivotal phase 3 study, Formulation B = rivoceranib 200 mg tablet/clinical formulation used in early clinical studies, Formulation C = rivoceranib 250 mg tablet/formulation to be developed for future use, Formulation D = rivoceranib 250 mg tablet/to-be-marketed formulation). Results: Of the 60 subjects enrolled, 66.7% were male, 88.3% were white, and median age was 43 years. The median plasma rivoceranib T max was similar following all treatments (2 hours post-dose). The 90% CIs around the geometric mean ratios (GMRs) of plasma rivoceranib AUC 0-t, AUC 0-inf , and C max for Formulation B vs. Formulation A and Formulation D vs. Formulation A were within the 80-125% reference interval, demonstrating bioequivalence between Formulation B and Formulation A as well as Formulation D and Formulation A. The 90% CIs around the GMRs of plasma rivoceranib AUC 0-t , AUC 0-inf , and C max for Formulation C vs. Formulation A were slightly outside of the 80%-125% reference interval. Conclusions: Formulations B (clinical formulation used in early clinical studies) and D (to-be-marketed formulation) were bioequivalent to Formulation A (clinical formulation used in the pivotal phase 3 study). Formulation C (formulation to be developed for future use) and Formulation A were similar, but the difference was slightly outside of the bioequivalence criteria. It remains to be evaluated whether the difference in bioavailability between Formulation C and Formulation A is clinically meaningful. Clinical trial information: NCT05287360 . [Table: see text]
Disease-free survival in operated patients with nmRCC using machine learning.
Authors: Gaëlle Margue, Loïc Ferrer, Guillaume Etchepare, Pierre Bigot, Karim Bensalah, Arnaud Mejean, Morgan Roupret, Nicolas Doumerc, Alexandre Ingels, Romain Boissier, Geraldine Pignot, Bastien Parier, Philippe Paparel, Thibaut Waeckel, Thierry Colin, Jean-Christophe Bernhard
Journal: Journal of Clinical Oncology (2023)

4539 Background: In patients operated for a non-metastatic renal cell carcinoma (nmRCC), risk evaluation of disease recurrence enables the therapeutic strategy to be adapted after surgery. Usual risk group stratification does not fully exploit the power of machine learning (ML) applied to multimodal data. We developed a ML model capable of calculating the risk of recurrence after surgery for nmRCC patients. Methods: A multicentric cohort of patients undergoing surgery between May 2000 and January 2020 for a nmRCC (pT any, N any, M0) was analyzed from data collected prospectively in the French research network on kidney cancer UroCCR (ClinicalTrials.gov: NCT03293563). Using clinical, biological, histological and radiological features, we developed a signature of patient-specific DFS. Participating medical centers were randomly assigned to training or validation cohorts with a 2:1 ratio of patients. The ML signature managed missing data using multiple imputation based on gradient boosted trees and chained equations. Several ML models were trained in a repeated 5x10-fold cross-validation procedure to optimize the integrated Area Under the ROC Curve (iAUC) between 0.5- and 5-years following surgery. The performance of the selected ML signature was then evaluated on the validation cohort and compared with usual risk scores. Results: 3354 patients were randomly assigned to a training cohort (n=2239 from 10 centers) and a validation cohort (n=1115 from 13 centers). Our risk score achieved an iAUC of 0.81 (0.76, 0.85) on the validation cohort and significantly outperformed the GRANT ( p &lt;0.001), SSIGN ( p =0.03), and UISS ( p &lt;0.001) risk scores. The Leibovich-2018 score was only defined in 51% of the patients, due to incomplete data. Permutation-based feature importance and Shapley values were used to estimate the contribution of each feature. The stratification of patients into four risk groups achieved an iAUC of 0.78 (0.74, 0.83) on the validation cohort. 190 (17%) patients were stratified in the low-risk group, with an actual 5-year DFS higher than 98% and no death observed within this horizon window. 188 (17%) patients were stratified in the high-risk group, with an actual 5-year DFS of 48%. Conclusions: The machine learning model estimating individual disease recurrence risk outperformed the predictive performances of usual risk scores while handling incomplete data in predictors. This could help in identifying patients for whom surveillance could be reduced and those who could be candidates for adjuvant therapies. [Table: see text]